Association between butyrylcholinesterase K variant and the Alzheimer type neuropathological changes in apolipoprotein E epsilon4 carriers older than 75 years.
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Age Factors↗
Biomedical subjects
N Suematsu
Publications and source records attributed to N Suematsu.
A deletion polymorphism of alpha(2)-macroglobulin gene and cerebral amyloid angiopathy.
BACKGROUND AND PURPOSE: alpha(2)-Macroglobulin may be implicated in amyloid beta protein deposition. A deletion in the exon 18 splice acceptor of the alpha(2)-macroglobulin gene (A2M) has been reported to be associated with risk for Alzheimer's disease (AD). In search of genetic risk factors for cerebral amyloid angiopathy (CAA), we investigated association of the A2M deletion polymorphism with CAA. METHODS: The association between the severity of CAA and A2M deletion polymorphism was investigated in 178 autopsy cases of the elderly including 68 patients with AD. RESULTS: There was no significant difference in the severity of CAA between individuals with the A2M deletion allele and those without in the AD, non-AD, or total cases. Status for the epsilon4 allele of the apolipoprotein E gene did not influence the results. CONCLUSIONS: Our results suggest that the A2M deletion polymorphism may not be a definitive risk factor of CAA in the elderly, although further study with larger samples is necessary to confirm this.
Aged↗
An immunohistochemical study of centenarian brains: a comparison.
To evaluate the pathology of centenarian brains, which would reflect the ultimate stage of the aging process, 13 centenarians (M:F=1:12; mean+/-SD, 101.5+/-1.5 years) from the consecutive autopsy series were studied. None had severe dementia compatible with Alzheimer's disease (AD). As younger controls, 20 nondemented (ND) individuals (79.8+/-3.2 years) and 20 AD patients (80.8+/-3.0 years) were selected. In addition to the routine examination including methenamine-Bodian staining, an immunohistochemical study was performed, using antibodies to amyloid beta protein, tau, ubiquitin, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-MIP (a marker of the microglial and perivascular cells). No centenarian subjects satisfied the neuropathological criteria for definite AD. The densities of senile plaques and neurofibrillary tangles (NFTs) were significantly lower in almost all examined subdivisions than the AD patients, and tended to be higher than the ND subjects. Cerebral amyloid angiopathy of the centenarian was less severe than the AD patients, as well as the proliterations of GFAP-positive astrocytes and Ki-MIP-positive microglial cells, and the loss of synaptic terminal density. The relative mildness of the age-related morphological changes in the centenarians compared with the AD patients supports the idea that AD would not be the ultimate condition of the aging process, but would develop through the switching to the pathological process.
Aged↗
Association of alpha1-antichymotrypsin polymorphism with cerebral amyloid angiopathy.
In search of genetic risk factors of sporadic cerebral amyloid angiopathy (CAA), we investigated the association of a polymorphism in the signal peptide sequence of alpha1-antichymotrypsin (ACT) with the severity of CAA in 155 autopsy cases of the elderly, including 48 patients with Alzheimer's disease. In the total cases, there was no significant association of the ACT genotypes (AA, AT, and TT) with the severity of CAA. Within the Alzheimer's disease group, however, a significant correlation was found between the ACT A allele frequency and the severity of CAA.
Aged↗
Production of prostaglandins E1 and E2 by adult human red blood cells.
We showed that human adult red blood cells (RBCs) produce prostaglandin E1 (PGE1) and E2 (PGE2). RBCs that were mechanically stressed in the presence of extracellular Ca2+ by being injected rapidly through a fine needle produced PGE1 and PGE2 within 30 min after this mechanical stress. The amounts of PGE1 and PGE2 produced by 1 x 10(9) mechanically stressed RBCs were approximately 50 pg and 100 pg, respectively, which were determined in the cytosolic fraction from sonicated RBCs using a competitive enzyme immunoassay method. A Western blot analysis using anti-cyclooxygenase-2 antibody revealed a band at the 70-kDa position in the samples from RBCs producing PGE1 and PGE2. Treatment with 10 micrograms/mL indomethacin completely inhibited the productions of PGE1 and PGE2. The present results may indicate a new role of RBCs in microcirculation.
Adult↗
Posterior interosseous nerve palsy.
Eleven patients with non-traumatic paralysis of posterior interosseous innervated muscles were divided into three types, and the association between the type of paralysis and sites of compression was investigated. Type 1 (drop finger and thumb) showed a simultaneous compression of the recurrent branch and the descending branch at the entrance point and within the supinator. Type 2 (drop fingers) had compression of the recurrent branch alone, and Type 3 (drop thumb) had compression of the descending branch alone. The exit point from the supinator is considered to be the site of compression in Types 2 and 3.
Adult↗
Presenilin 1 intronic polymorphism is not associated with Alzheimer type neuropathological changes or sporadic Alzheimer's disease.
BACKGROUND: A genetic association between the presenilin 1 (PS-1) intronic polymorphism and sporadic Alzheimer's disease has been a matter of controversy. Recent findings have suggested that the PS-1 polymorphism is not associated with Alzheimer's disease or amyloid beta-protein (Abeta) deposition in brains from patients with Alzheimer's disease. OBJECTIVES: To elucidate the influence of the PS-1 polymorphism on Alzheimer type neuropathological changes and the development of Alzheimer's disease, the relation between the PS-1 polymorphism and quantitative severity of Alzheimer type neuropathological changes in the brains from patients with Alzheimer's disease and non-demented subjects was studied. METHODS: The PS-1 and apolipoprotein E (ApoE) genotypes, were examined, together with the densities of the senile plaques, senile plaques with dystrophic neurites, and neurofibrillary tangles in the brains from 36 postmortem confirmed patients with sporadic Alzheimer's disease and 86 non-demented subjects. Association of the PS-1 polymorphism with sporadic Alzheimer's disease and ages at onset and duration of illness in Alzheimer's disease was also examined. RESULTS: The PS-1 polymorphism was not associated with the senile plaques, senile plaques with dystrophic neurites, or neurofibrillary tangles in Alzheimer's disease or non-demented subjects. There was no association of the PS-1 intronic polymorphism with Alzheimer's disease, ages at onset, or durations of illness in Alzheimer's disease. The results remained nonsignificant even when the PS-1 genotype groups were divided into the subgroups with different ApoE epsilon4 status. CONCLUSIONS: The PS-1 intronic polymorphism does not itself have a direct causal role in the formation of Alzheimer type neuropathological changes or in the development of sporadic Alzheimer's disease.
Age of Onset↗
Butyrylcholinesterase K variant and cerebral amyloid angiopathy.
BACKGROUND AND PURPOSE: Cholinesterases are found histochemically in the vessels affected with cerebral amyloid angiopathy (CAA). A gene for the K variant of butyrylcholinesterase (BCHE-K) may be associated with late-onset Alzheimer's disease (AD). In search of genetic risk factors for CAA, we investigated the association of BCHE-K with CAA. METHODS: The association between the severity of CAA and BCHE-K was investigated in 155 autopsy cases of the elderly, including 48 patients with AD. RESULTS: There was no significant association of BCHE-K with the severity of CAA in the total, AD, or non-AD cases. Status of the epsilon4 allele of apolipoprotein E gene did not influence the results. CONCLUSIONS: Our results may suggest that BCHE-K is not a definitive risk factor for CAA in the elderly, although further study with larger samples is necessary to confirm this.
Aged↗
Panencephalopathic type of Creutzfeldt-Jakob disease associated with cadaveric dura mater graft.
A 52 year old man with Creutzfeldt-Jakob disease who received a cadaveric dura mater graft 99 months before the onset is reported. The prion protein gene was homozygous for methionine at the polymorphic codon 129. Neuropathological examination disclosed a panencephalopathic type of Creutzfeldt-Jakob disease which was characterised by severe involvement of the cerebral white matter and cerebellum, as well as of the cerebral cortical and deep grey matter. Thus the panencephalopathic type of Creutzfeldt-Jakob disease may occur in association with cadaveric dura mater grafts.
Cadaver↗
Association of presenilin-1 polymorphism with cerebral amyloid angiopathy in the elderly.
BACKGROUND AND PURPOSE: An intronic polymorphism of presenilin-1 (PS-1), a gene responsible for early-onset familial Alzheimer's disease, has been reported to be associated with late-onset sporadic Alzheimer's disease. In a search for a genetic risk factor of sporadic cerebral amyloid angiopathy (CAA), we investigated the association of the polymorphism of PS-1 with CAA. METHODS: The association between the severity of CAA and genotypes of a polymorphism in intron 8 of PS-1 was investigated in 137 autopsy cases of the elderly. RESULTS: A significant decrease of PS-1 2/2 genotype frequency was associated with severe or moderate CAA. CONCLUSIONS: Our results suggest that PS-1 intronic polymorphism may be associated with the severity of CAA in the elderly.
Aged↗
Lack of an association between apolipoprotein E epsilon 4 and cerebral amyloid angiopathy in elderly Japanese.
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Aged↗
Apolipoprotein E genotype in elderly nondemented subjects without senile changes in the brain.
Only a small minority of elderly subjects can survive with a brain free of senile changes (senile plaques, neurofibrillary tangles, and amyloid angiopathy) beyond the age of 80 years. We demonstrated that an increase of epsilon 2 allele frequency and a decrease of epsilon 4 allele frequency of the apolipoprotein E gene are associated with such brain aging without senile changes.
Aged↗
Dementia characterized by abundant neurofibrillary tangles and scarce senile plaques: a quantitative pathological study.
We report an elderly case who had demonstrated progressive memory disturbance and disorientation for 4 years. The clinical features were indistinguishable from late-onset dementia of the Alzheimer type (DAT). Neuropathologically, however, senile plaques (SPs) were almost absent throughout the brain. In contrast, numerous neurofibrillary tangles (NFTs) were observed in the hippocampus and neighboring regions, with much higher density than age-matched normal controls. The immunohistochemical and ultrastructural properties of the NFTs were identical to those of typical DAT. The present case is histologically different from DAT because of the scarce SPs and indicates that numerous NFTs in the hippocampal region can be formed independently of the existence of SPs.
Aged↗
Influence of apolipoprotein E genotype on cerebral amyloid angiopathy in the elderly.
BACKGROUND AND PURPOSE: The inheritance of the epsilon 4 allele of the apolipoprotein E gene (APOE) is associated with increased risk of developing dementia of the Alzheimer type (DAT). We have investigated whether the APOE genotype influences the severity of cerebral amyloid angiopathy (CAA) in elderly individuals with or without DAT. METHODS: From a consecutive autopsy series, we studied 88 patients (85.2 +/- 8.1 years) without degenerative disorders other than DAT. The percentages of amyloid-laden vessels in the occipital lobes were calculated and compared between APOE genotypes. RESULTS: For epsilon 3/3 and epsilon 3/4 genotypes, there was a trend toward increased CAA in epsilon 3/4 individuals for non-DAT and conversely in epsilon 3/3 individuals for DAT patients, but these did not achieve significance. CONCLUSIONS: The present study suggests that the epsilon 4 allele is not a strong risk factor for CAA in elderly people.
Aged↗
Immune reactions associated with cerebral amyloid angiopathy.
BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) occasionally coexists with cerebral vasculitis. An immune system may influence deposition or degradation of the amyloid in cerebral blood vessels. The purpose of this study was to elucidate immune reactions associated with CAA. METHODS: In 11 elderly patients with sporadic CAA, 2 patients with Icelandic familial CAA, and 2 patients with CAA and granulomatous angiitis, the cerebrovascular amyloid proteins and infiltrating inflammatory cells were analyzed immunohistochemically. RESULTS: In both sporadic CAA (beta-protein amyloid angiopathy) and Icelandic familial CAA (cystatin C amyloid angiopathy), leptomeningeal and cortical vessels were associated with an increase or activation of monocyte/macrophage lineage cells. In the cases of CAA with granulomatous angiitis, the vascular amyloid was of beta-protein and associated with infiltration of many monocyte/macrophage lineage cells, which included multinucleated giant cells containing the amyloid in the cytoplasm as well as T cells composed of CD4+ and CD8+ subsets. Amyloid P component, which was reported to be a common component of amyloid deposits and to prevent phagocytic proteolysis of amyloid fibrils of beta-protein, was negative for the vascular amyloid in a case of CAA with granulomatous angiitis but positive in the others. CONCLUSIONS: In both the beta-protein and cystatin C amyloid angiopathies, cerebrovascular amyloid deposition was associated with an increase or activation of monocyte/macrophage lineage cells. Prominent reactions of monocyte/macrophage lineage cells admixed with CD4+ and CD8+ T cells (granulomatous angiitis) were occasionally associated with beta-protein angiopathy. In some of these cases, the absence of amyloid P component might be related to pathogenesis of the granulomatous reaction.
Aged↗
Quantitative characterization of P-glycoprotein-mediated transport in mdr1-gene-transfected lymphoma cells.
We have established a quantitative flow cytometry system to elucidate the causal role of P-glycoprotein in the phenomenon of multidrug resistance. We have used this method to analyze the accumulation and release of adriamycin (ADM) in intact L5178Y and L5178Y/VMDR/C.06 (L5178Y/R) cells, by determining the effect of sodium orthovanadate (Na3VO4), verapamil, bovine serum albumin (BSA) and physiologically operative materials on the cells. Based on the experiments, we prepared a standard solution that contained NaCl, D-glucose, L-cysteine, HCO3- and BSA, which was sufficient to perform transport experiments. In particular, BSA caused a decrease in ADM accumulation and a facilitation of the rate of ADM release in both L5178Y and L5178Y/R cells, probably due to its relatively high affinity for ADM as compared to the cell membrane. In multidrug-resistant L5178Y/R cells, sodium orthovanadate, a strong ATP-binding inhibitor, caused a marked increase in the accumulation of ADM, whereas vanadate-treated drug-sensitive L5178Y cells showed little increase in ADM accumulation. In a release (0-trans exit) experiment, vanadate-treated L5178Y/R cells exhibited an apparent decrease in ADM release (increase in ADM retention), to a level which was almost the same as L5178Y cells. We thus confirmed that the P-glycoprotein-mediated efflux system is coupled with P-glycoprotein-associated ATP-hydrolysis. Further, verapamil, a potent inhibitor of P-glycoprotein-mediated transport, facilitated the ADM accumulation in L5178Y/R cells up to the level of L5178Y and vanadate-treated L5178Y/R cells. A more important finding is that, in the release experiment, verapamil-treated L5178Y/R cells exhibited a much greater ADM retention than drug-sensitive L5178Y and vanadate-treated L5178Y/R cells. These findings, in particular the potent effect of verapamil on drug-resistant cells, may afford new insight into the pathophysiology of the phenomenon of multidrug resistance and the mechanism of action of the multidrug transporter.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Glucose metabolism and Alzheimer's dementia].
Blood glucose levels are abnormally low in Alzheimer's dementia. We therefore examined glucose metabolism before death in relation to Alzheimer's dementia as determined at autopsy in 106 men and 161 women. The mean age was 81.8 +/- 8.6 years for men and 85.8 +/- 7.9 years for women (p < 0.001). The fasting plasma glucose level and hemoglobin Alc levels did not differ by sex. Alzheimer's dementia was detected in 88 patients (25.5%). More women than men had the disease, but the difference was not significant. Only 8.8% (3/34) of patients with diabetes mellitus had Alzheimer's dementia, as compared with 27.9% of patients without diabetes mellitus (65/233, p < 0.03). The fasting plasma glucose level was 89.9 +/- 13.4 mg/dl in patients with Alzheimer's dementia and 102.9 +/- 34.5 mg/dl in those without the disease. The hemoglobin Alc level was 5.7 +/- 0.8% in patients with Alzheimer's dementia and 6.4 +/- 1.5% in those without the disease. Both the fasting glucose level and hemoglobin Alc level were significantly lower in patients with Alzheimer's dementia than in those without the disease, p < 0.01. These data suggest that the development of Alzheimer's dementia is suppressed by the high plasma glucose levels in patients with diabetes mellitus.
Aged↗
A case with intractable pain suffering from pancoast syndrome.
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Journal Article↗